Bisphosphonate Delivery to Tubular Bone Allografts

Abstract

Large structural allografts used for reconstruction of bone defects after revision arthroplasty and tumor resection fracture up to 27% of the time from osteolytic resorption around the fixation screw holes and tendon or ligament attachment sites. Treating structural allografts before implantation with bisphosphonates may inhibit local osteoclastic processes and prevent bone resorption and the development of stress risers, thereby reducing the long-term fracture rate. Taking advantage of allografts' open-pore structure, we asked whether passive soaking or positive-pressure pumping was a more efficient technique for delivering bisphosphonates. We treated matched pairs of ovine tibial allografts with fluids containing Tc-99m pamidronate and toluidine blue stain to facilitate indicator distribution analysis via microSPECT-microCT imaging and light microscopy, respectively. Surfactants octylphenoxy polyethoxy ethanol or beractant were added to the treatment fluids to reduce flow resistance of solutions pumped through the allografts. Indicator distribution after 1 hour of soaking produced a thin ring around periosteal and endosteal surfaces, while pumping for 10 minutes produced a more even distribution throughout the allograft. Flow resistance was reduced with octylphenoxy polyethoxy ethanol but unaffected with beractant. Pumped allografts displayed a more homogeneous indicator distribution in less time than soaking while surfactants enhanced fluid movement.

Distribution of Locally Delivered Antimicrobials Is Limited by Cortical Bone: A Pilot Study

“…These three segmental types represent the major regions of human long bones. The lack of fluorescence visualization over smooth areas free of vascular foramina is consistent with DiResta et al [3] who reported minimal penetration of cortical bone from the endosteal surfaced after 1 hour of passive diffusion or incomplete penetration after 20 minutes of pressurized infusion in an ovine tibial model. They pressurized an intramedullary infusion of toluene blue and Tc-99m-labeled pamidronate with a surfactant, up to +250 mm Hg, with simultaneous application of extraosseous vacuum at À50 mm Hg.…”

“…Third, we did not directly examine the distributions of vancomycin or doxycycline in the substance of cortical bone. The pattern and extent of penetration that can occur under passive diffusion or from artificially driven convection has been reported by Elson et al [4] and DiResta et al [3]. Fourth, the cleaned cadaver bone had all soft tissues removed, which could have potentially increased the transport of antimicrobials through the vascular foramina.…”

“…Neither the transcortical elution in our study nor that in the study by Elson et al [4] addresses how the antimicrobial gets into the extraosseous fluid. DiResta et al [3] studied penetration into cortical bone but not transport through the full cortical thickness to the opposite surface or transport into the extraosseous compartment.…”

Antimicrobial Distribution From Local Delivery Depends on Dose

“…Soft tissue is expected to have higher clearance than sites within bone. Therefore, the duration of high levels may be shorter than what would be expected from spacers that are surrounded by bone [11,24]. The difference in delivery sites, soft tissue versus bone, is not addressed by this study or the study by Adams et al [1].…”

Intercalary Allograft Reconstructions Using a Compressible Intramedullary Nail: A Preliminary Report

“…Allograft fixation has been performed by various methods, typically consisting of plates and screws [18,19,22,30], intramedullary devices [1,7,18,19,30,33,34], or a combination [18,33]. Alternative and additional strategies to enhance union include autogenous bone grafting [9], autogenous bone marrow aspirate [28], bone morphogenic protein [5], bisphosphonate treatment [6], and electromagnetic field exposure [4]. Each method of fixation and augmentation has benefits and drawbacks.…”